Advances in Heart Failure_Drugs to Devices.pptx

recent advances in management of hfref in terms of drugs & devices has significantly brought down mortality & improved qol in these sick patients.
NEW DEVICES HAV MADE POSSIBLE EVEN IN PATIENTS WITH END STAGE HEART FAILURE TO LIVE WITHOUT A TRANSPLANT

1. Advances in Heart Failure: Drugs to Devices

2. Heart Failure (HF) Is a Growing Clinical Burden AHA 2016 Statistics at a Glance, 2016. Krumholz HM, et al. Patterns of hospital performance in acute myocardial infarction and heart failure 30-day mortality and readmission. Circ Cardiovasc Qual Outcomes . 2009; 2:407-13. Heidenreich PA, et al. Forecasting the impact of heart failure in the United States. A policy statement from the American Heart Association. Circ Heart Fail . 2013; 6: 606-619. HIGH INCIDENCE, HIGH PREVALENCE AND POOR PROGNOSIS despite advances in the treatment of HF over the past few decades PREVALENCE 2.2% prevalence 1 5.7M HF patients 1 Projected to increase to > 8M people ≥ 18 years of age with HF by 2030 1 INCIDENCE 915,000 people ≥ 45 years of age are newly diagnosed each year with HF 1 MORBIDITY AND MORTALITY For AHA/ACC Stage C/D patients diagnosed with HF : 50% readmitted within six months 2 50% will die within five years 3 ACC = American College of Cardiology AHA = American Heart Association UNITED STATES 33668-SJM-CRM-0819-0243 | Item approved for global use. Prevalence of HF in India - 10 million or about 0.9% of the total population HF burden due to MI - 2.1 million to 8.4 million (estimate of about 4–5 million ) HF due to HT - 3.5–7 million (estimate of about 4–5 million) Annual mortality due to HF - 0.1–0.16 million

3. Heart Failure – A Bigger Challenge in India Mean Age of Patients: 53 Years In-Hospital Mortality: 30.8% Post Discharge Mortality (6 months): 26.3% Global India Mean Age of Patients: 73 Years In-Hospital Mortality: 3.8% Post Discharge Mortality (6 months): 8.6% Patients With Heart Failure In India Affected at a Younger Age Have a Very High Mortality Both In-Hospital and also After Discharge Seth S, et al. J Pract Cardiovasc Sci 2015;1:35-8. For the use only of healthcare practitioner, hospital, or laboratory Natural History of CHF

4. STROKE VOLUME PRELOAD AFTERLOAD CONTRACTILITY CARDIAC OUTPUT HEART RATE VENTRICULAR D YSSYNCHRONY CRT MITRAL REGURGITATION Therapeutic Approaches To Heart Failure Diuretics Digitalis ACE-Inhibitor ARB ‘ s Renin Inhibitor ß-Blockers Aldosterone Antagonist Mitra- Clip 33668-SJM-CRM-0819-0243 | Item approved for global use.

5. Paradigm Shifts in Heart Failure Hybrid Therapy Sacks CA, et al. N Engl J Med 2014;371:1062–4 For the use only of healthcare practitioner, hospital, or laboratory Digoxin Diuretics Hydralazine + ACE Inhibitors + β Blockers + Aldosterone Inhibitors Unmet Need Mortality - 23% - 35% - 22% Heart Failure: pharmacotherapies are effective, but mortality remains substantial

6. The Mortality Benefit of Vymada HR=0.84 (95% CI: 0.76–0.93) p=0.001 HR*=0.80 (95% CI: 0.71–0.89) p<0.001 HR=0.80 (95% CI: 0.68–0.94) p=0.008 HR=0.79 (95% CI: 0.64–0.98) p=0.034 Cause of death Number of deaths 300 200 400 500 700 600 800 900 All causes CV causes Sudden cardiac death Worsening heart failure 100 711 835 693 558 311 250 184 147 Vymada (N=4,187) Enalapril (N=4,212) *Results from death from CV causes as per those reported by McMurray et al. Note that the hazard ratio reported by Desai et al. was HR=0.80 (95%CI: 0.72 –0.89); p<0.001 ACEI=angiotensin-converting-enzyme inhibitor; ARNI=angiotensin receptor neprilysin inhibitor; CI=confidence interval; CV=cardiovascular; HFrEF =heart failure with reduced ejection fraction; HR=Hazard ratio; PARADIGM-HF=Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure 1.Desai et al. Eur Heart J 2015; epub ahead of print: DOI:10.1093/ eurheartj /ehv186; 2.O’Connor et al. Am J Cardiol 1998;82:881–7 The majority (>80%) of deaths in PARADIGM-HF had a CV cause 1 The mortality benefit of Vymada is related to the observed reduction in sudden cardiac death and death due to worsening heart failure 1 This distribution of cause of death in PARADIGM-HF is comparable to recent HFrEF trials 2 For the use only of healthcare practitioner, hospital, or laboratory

7. HF – Reduced ejection fraction Fonarow G C et al. J Am Heart Assoc 2012;1:16-26 LVEF % SCA Victims 7.5% 5.1% 2.8% 1.4%

8. Lack Of AV And V-to-V Synchrony Result In Poor Cardiac Function Mitral regurgitation Improper LV filling Sub-optimal atrial filling Delayed LV contraction Abnormal septal motion ENLARGED HEART 33668-SJM-CRM-0819-0243 | Item approved for global use.

9. Electrical Dyssynchrony vs. Mechanical Dyssynchrony Dyssynchrony can be described as electrical, with prolonged QRS duration, or mechanical, with an abnormal contraction pattern. 9 April 2022 Heart Failure: Disease Overview/ Guidelines for CRT Implantation

10. QRS Duration (msec) <90 90-120 120-170 170-220 >220 Wide QRS – Proportional Mortality Increase NYHA Class II-IV patients 3,654 ECGs digitally scanned Age, creatinine, LVEF, heart rate, and QRS duration found to be independent predictors of mortality Relative risk of widest QRS group 5x greater than narrowest 1 Gottipaty V, Krelis S, Lu F, et al. JACC 1999;33(2) :145 [Abstr847-4]. Vesnarinone Study 1 (VEST study analysis)

11. 11 April 2022 Heart Failure: Disease Overview/ Guidelines for CRT Implantation Left Bundle Branch Block (LBBB)

12. Increased Mortality Rate with LBBB Increased 1-year mortality with presence of complete LBBB (QRS > 140 ms ) Risk remains significant even after adjusting for age, underlying cardiac disease, indicators of HF severity, and HF medications Baldasseroni S, Opasich C, Gorini M, et al. Am Heart J 2002;143:398-405 11.9 5.5 16.1 7.3 5 10 15 20 All Cause Sudden Cardiac All patients N=5517 LBBB N=1391 HR * 1.70 (1.41-2.05) HR * 1.58 (1.21-2.06) Cause of Death 1-Year Mortality (%) * HR = Hazard Ratio

13. Cardiac Resynchronization Therapy is the placement of an ADDITIONAL PACING LEAD on the LEFT SIDE of the heart 33668-SJM-CRM-0819-0243 | Item approved for global use.

14. COMPARED TO OPTIMAL PHARMACOLOGICAL THERAPY, CRT: Improves EF, NYHA Class and 6 MWT results 1 Reduces rates of all-cause, cardiac, and HF hospitalization 2 COMPARED TO TRADITIONAL ICD THERAPY, CRT: Decreases hospitalizations 3 Reduces the risk of death 4 Benefits of Cardiac Resynchronization Therapy Abraham WT, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002 Jun;346(24):1845-53. Anand IS, et al. Cardiac resynchronization therapy reduces the risk of hospitalizations in patients with advanced heart failure: results from the Comparison of Medical Therapy, Pacing and Defibrillation In Heart Failure (COMPANION) trial. Circulation. 2009 Feb 24;119(7):969-77. Tang AS, Resynchronization-Defibrillation for Ambulatory Heart Failure Trial Investigators, et al.Cardiac -resynchronization therapy for mild-to-moderate heart failure. N Engl J Med. 2010 Dec 16;363(25): 2385-95. Epub 2010 Nov 14. Cleland JG, Daubert ,Cardiac Resynchronization- Heart Failure (CARE-HF) Study Investigators, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49. CRT BENEFITS HF PATIENTS WITH A WIDE QRS AND LOW LVEF

15. Who Can Benefit From CRT? HEALTHY HEART ENLARGED HEART Approximate 40% HEART FAILURE PATIENTS, specifically those with inter- or intra-ventricular conduction delays (IVCDs) 33668-SJM-CRM-0819-0243 | Item approved for global use.

16. Device Goals of Cardiac Resynchronization Therapy Overall goal is to IMPROVE CARDIAC OUTPUT CRT provides options: Restore appropriate AV Synchrony Electrically Restore Mechanical Ventricular Synchrony Improve symptoms and quality of life Decrease likelihood of disease progression; possibly reverse remodel Complement drug therapy 33668-SJM-CRM-0819-0243 | Item approved for global use.

17. Summary of CRT Mechanisms Yu C-M, Chau E, Sanderson J, et al. Circulation 2002;105:438-445 Intraventricular Synchrony Atrioventricular Synchrony Interventricular Synchrony  LA Pressure  LV Diastolic Filling  RV Stroke Volume  LVESV  LVEDV Reverse Remodeling Cardiac Resynchronization  MR  dP/dt,  EF,  CO (  Pulse Pressure)

18. Indications for CRT Therapy 1 NOTE: Colors correspond to the Class of Recommendations (CORs) in the ACCF/AHA Table 1. 1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of CardiologyFoundation /American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol . 2015;62(16):e147-e239. CLASS 1 (Should be performed) CLASS IIa (Is reasonable to perform) CLASS IIb (May/might be reasonable) CLASS III (No benefit) 33668-SJM-CRM-0819-0243 | Item approved for global use. NYHA CLASSES

19. Summary: ACCF/AHA/HRS HF Guidelines CRT-D indicated HF NYHA II/III/IV? Yes No QRS > 150 ms? Yes No EF < 35%? Yes No All patients on optimal medical therapy Reasonable expectation of survival >1 year? LBBB Level of Evidence: B Level of Evidence: A LBBB with a QRS duration 120 to 149 ms Class IIa:

20. NYHA Classes III & IV Patients have been the initial focus, reported stunning results in initial Trials 19% reduction in mortality + HF hospitalisations with CRT 24% reduction in all-cause mortality with CRT-D 40% reduction in all-cause mortality with CRT 37% reduction in mortality or CV hospitalisations with CRT 2002 MIRACLE 2005 CARE-HF 2004 COMPANION 40% reduction in major clinical events and hospitalisations with CRT in NYHA III & IV

21. Randomised Controlled Trials of CRT in Less Symptomatic, Wide QRS Heart Failure Contak CD* MIRACLE ICD II REVERSE MADIT CRT RAFT ‘03 ‘ 04 ‘05 ‘ 06 ‘07 ‘ 08 ‘09 ‘ 10 Actual Forecasted CARE-HF* Nearly 5000 mildly symptomatic patients have been enrolled in randomised controlled trials to date In this population, cardiac resynchronisation therapy limits the progression of heart failure Follow-up (Months) * NYHA Class I and II during run-in period. Contak CD* CARE-HF* REVERSE (Europe) MIRACLE ICD II REVERSE MADIT CRT

22. Readmission & Mortality Poor outcomes are common for patients after hospitalization for heart failure (HF): 50% 35% Kosiborod et al. Am J Med . 2006;119:616.e611– 616.e617. Rathore et al. Am Heart J . 2006;152:371–378. 1-Year Readmission Rates 1-Year Mortality

23. Readmission & Mortality Poor outcomes are common for patients after hospitalization for heart failure (HF): 50% 35% Kosiborod et al. Am J Med . 2006;119:616.e611– 616.e617. Rathore et al. Am Heart J . 2006;152:371–378. 1-Year Readmission Rates 1-Year Mortality Cardiac Resynchronization Therapy (CRT) is associated with 50% reduction in hospitalization 36% reduction in mortality

24. CRT Is Highly Beneficial CRT is an effective treatment for heart failure patients with: systolic dysfunction ventricular electrical conduction delays Mortality HF or CV hospitalizations Cardiac Function/ Structure QoL or NYHA CARE-HF 1,2 + + + NA COMPANION 3 + + NA NA MIRACLE 4 NA NA + + MIRACLE ICD 5 NA NA NA + REVERSE 6 NA +* + = RAFT 7 + + NA NA MADIT CRT 8 + * + +* NA 1 Cleland J, et al. N Engl J Med . 2005;352:1539-1549. 2 Cleland J, et al. Eur Heart J . 2006;27:1928-1932. 3 Bristow M, et al. J Card Fail. 2000;6:276-285. 4 Abraham W, et al. N Engl J Med . 2002;346:1845-1853. 5 Young J, et al. JAMA . 2003;289:2685-2694. 6 Linde C, et al. JACC . 2008;52:1834-1843. 7 Tang A, et al. N Engl J Med . 2010;363:2385-2395. 8 Moss A, et al. N Engl J Med . 2009;361:1329-1338. NA = Not powered, not collected, or not blinded for specific end point. * Post-hoc analysis.

25. Efforts shifted to Milder CHF post Care-HF First randomized trial on CRT First randomized CRT-D trial on NYHAII First randomized CRT trial showing mortality and morbidity benefits on NYHAIII&IV First randomized CRT trial showing mortality and morbidity benefits on NYHAII 2002 MIRACLE 2004 MIRACLE ICD II 2005 CARE-HF 2009 REVERSE 2010 RAFT Determine mortality and morbidity benefits of CRT-D vs ICD only in mild/moderate HF patients

26. Daubert et al. J Am Coll Cardiol 2009;Vol 54, No 20 REVERSE 24-months: first trial showing reduction in time to first HF hospitalization or death… Number at Risk CRT OFF 82 79 76 70 39 CRT ON 180 176 173 168 77 62% reduction with CRT CRT in NYHAII produces similar benefits than those in NYHA III-IV

27. …associated with a relevant heart remodeling effect: CRT reversing the progress? LVESV 0 ml -27 ml p<0.001 Change from baseline in ml LVEF Change from baseline in % units p<0.001 2% 7% CRT-ON CRT-OFF CRT-ON CRT-OFF CRT in NYHAII produces similar benefits than those in NYHA III-IV Daubert et al. J Am Coll Cardiol 2009;Vol 54, No 20

28. Making Ventricular Pacing more Physiologic: Stimulating Conduction System Directly 29

29. Left Bundle Branch Pacing

30. Left bundle branch–optimized cardiac resynchronization therapy (LOT-CRT) (Heart Rhythm 2022;19:3 – 11) LOT-CRT is feasible and Safe and Provides greater electrical resynchronization as compared with BiV -CRT and could be an alternative, especially for Suboptimal CRT’s Echocardiographic Response QRSd Across Modalities LBBAP-optimized CRT (LOT-CRT) was attempted in Non-consecutive patients with CRT indications.

31. Response of functional MR in NICM to LBBB Pacing Heart Rhythm, Vol 19, No 5, May 2022 Shunmuga Sundaram Ponnusamy , MD, DM, CEPS,* Thabish Syed, MBBS, DNB,* Pugazhendhi Vijayaraman , MD, FHRS† Group I with mild FMR Group II with significant FMR LBBP resulted in excellent electrical resynchronization, with significant reduction in FMR severity in the majority of patients with significant FMR

32. | 33 Current HRSGuidelines HF Indication:
Selective pt population (2b) In case of failed CRT (2a)

33. SCD Rates in CHF Patients with LV Dysfunction Total mortality ~15-40%; SCD accounts for ~50% of the total deaths. 12 months 16 months 41.4 months 27 months 13 months 45 months 6 months Control Group Mortality % Patients with HF are overall at 6-9 times higher risk for SCD than general population

34. Modes of Death in Congestive Heart Failure (CHF) 1 MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). Lancet . 1999;353:2001-07. CHF Other Sudden Death 33668-SJM-CRM-0819-0243 | Item approved for global use.

35. Secondary Prevention of SCA Dickstein et al. Eur Heart J. 2008. DOI:10.1093/eurheartj/ehn309 LV EF < 40%? Yes No Documented haemodynamically unstable VT and/or VT with syncope? Yes No Survivor of ventricular fibrillation? Yes No ICD Level IA Level IA ICD All patients on optimal medical therapy with life expectancy >1 year

36. Dickstein et al. Eur Heart J. 2008. DOI:10.1093/eurheartj/ehn309 >40 days past MI? Yes No Nonischaemic heart disease? Yes No EF ≤35%? Yes No EF ≤35%? Yes No Level IA NYHA II/III Yes No Level IB All patients on optimal medical therapy with life expectancy >1 year ICD ICD Primary Prevention of SCA in LV Dysfunction

37. Mitral Regurgitation (MR) Occurs when the mitral valve fails to close tightly, allowing blood to flow backwards into the heart. Severity scale of 1+ (mild) to 4+ (severe) Two kinds: Degenerative MR (DMR) - includes stretching or rupture of the chordae tendineae . Funtional MR (FMR) - normal valve anatomy; impaired ventricular wall function and dilation.